Effect of TGF-ß1 on myocardial cell apoptosis in rats with acute myocardial infarction via MAPK signaling pathway.

OBJECTIVE: Transforming growth factor beta 1 (TGF-ß1) can promote myocyte hypertrophy, thus playing an important role in ventricular remodeling after myocardial infarction (MI). MATERIALS AND METHODS: In this study, the model of MI was established in rats through ligating the left anterior descending coronary artery. Subsequently, the messenger ribonucleic acid (mRNA) and protein expression levels of TGF-ß1 in myocardial cells in both model group and sham operation group were determined. The effects of TGF-ß1 treatment on myocardial cell apoptosis in MI rats were explored. Moreover, the changes of mitogen-activated protein kinase (MAPK) signaling pathway in rats with acute MI were verified. In addition, the protein expressions of phosphorylated-MAPK kinases 3/6 (p-MKK3/6) and MKK3/6 in myocardial cells of the two groups were analyzed. RESULTS: The mRNA and protein expression levels of TGF-ß1 in myocardial cells of acute MI rats were significantly higher than those in the sham operation group (p<0.01). After treatment with TGF-ß1, the expression level of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax) was obviously down-regulated. The Bax/Bcl-2 ratio was notably lower than that in control group (p<0.01). Meanwhile, the proportion of apoptotic cells decreased remarkably (p<0.01). In the model group, no evident change was observed in the protein expression level of MKK3/6, whereas the levels of p-MKK3/6 were prominently up-regulated (p<0.01). CONCLUSIONS: TGF-ß1 can activate MKK3/6 in the MAPK signaling pathway to resist the apoptosis of myocardial cells in acute MI rats.

Coagulase-negative staphylococcal meningitis in adults: clinical characteristics and therapeutic outcomes.

BACKGROUND: We wanted to analyze the clinical characteristics and therapeutic outcomes of adult meningitis caused by coagulase-negative staphylococci (CoNS). PATIENTS AND METHODS: Over a period of 5 years (January 1999 to December 2003), 127 cases were identified as having adult culture-proven bacterial meningitis caused by a single pathogen. Of them, 14 cases with CoNS meningitis were enrolled, and their clinical characteristics and therapeutic outcomes were analyzed. RESULTS: The 14 cases (median age 37.5; range 24-77 years old) included nine men and five women. With polynerase chain reaction sequencing of bacterial 16S r-RNA, 10 of the 14 CoNS strains were identified as Staphylococcus epidermidis infection, and the other four belonged to Staphylococcus haemolyticus. All 14 cases were in a postneurosurgical state with insertion of a ventriculoperitoneal shunt, external ventricular device or intrathecal port A as their underlying conditions, and 12 of the 14 patients contracted the infection nosocomially. Fever (86%), leukocytosis (79%), hydrocephalus (50%), consciousness disturbance (36%), and seizure (7%) were the major clinical manifestations. All the involved CoNS strains showed resistance to oxacillin but retained their susceptibility to vancomycin and linezolid. All 14 CoNS strains had positive mecA gene detection. With the removal of neurosurgical devices and intravenous vancomycin therapy, 86% (12/14) of the patients survived. CONCLUSION: CoNS meningitis accounted for 11% (14/127) of our adult bacterial meningitis. All adult CoNS meningitis patients had a disrupted barrier of the central nervous system as the underlying condition. S. epidermidis was the most common CoNS subtype involved. All involved CoNS strains were oxacillin resistant. The therapeutic result showed that adult CoNS meningitis had a mortality rate of 14% (2/14).

Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea.

We investigated the mechanisms of action of S-petasin and S-isopetasin, from Petasites formosanus Kitamura which is used as a folk medicine for treating hypertension, tumors, and asthma in Taiwan. The tension changes of tracheal segments were isometrically recorded on a polygraph. S-Petasin and S-isopetasin non-competitively inhibited cumulative histamine-, and carbachol-induced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a competitive manner. S-Petasin also non-competitively inhibited cumulative Ca(2+)-induced contractions in depolarized (K+, 60 mM; histamine, 100 microM; or carbachol, 10 microM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 microM)-remaining tension of carbachol (0.2 microM)-induced precontraction was further relaxed by S-petasin or S-isopetasin, suggesting that no matter whether either blocked VDCCs or not, S-petasin or S-isopetasin may have other mechanisms of relaxant action. The relaxant effect of S-petasin or S-isopetasin was unaffected by the presence of propranolol (1 microM), 2',5'-dideoxyadenosine (10 microM), methylene blue (25 microM), glibenclamide (10 microM), N omega-nitro-L-arginine (20 microM), or alpha-chymotrypsin (1 U/ml). However, S-petasin (100-300 microM), but not S-isopetasin, significantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trachealis. The above results reveal that the mechanisms of relaxant action of S-petasin and S-isopetasin may be primarily due to its non-specific antispasmodic and antimuscarinic effects, respectively.

Relaxant effects of petasins in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare four petasins, isolated from Petasites formosanus Kitamura, and to look for structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 microM)-, carbachol (0.2 microM)-, KCl (30 mM)-, and leukotriene D4 (10 nM)-induced precontractions of isolated guinea pig trachealis. The IC50 values strongly showed that the relaxant effects of the sulfur-containing petasins, S-petasin and S-isopetasin, were more potent than those of non-sulfur-containing petasins, petasin and isopetasin. S-isopetasin, with IC50 values around 10 microM, selectively relaxed carbachol- and KCl-induced precontractions, and had almost no effects (IC50s > 300 microM) on histamine- and leukotriene D4-induced precontractions. However, S-petasin, with IC50 values about 6-9 microM, non-selectively relaxed the precontractions induced by all these contractile agents. The influence of isomerization of either petasin to isopetasin or S-petasin to S-isopetasin on the relaxant effects is not clear.